Epicatechin oligomers longer than trimers have anti-cancer activities, but not the catechin counterparts

Abstract Since procyanidins (oligomeric catechin or epicatechin) were reported to exhibit health benefits, much attention has been paid to the synthesis of these compounds, especially those that are longer than trimers. In the present study, syntheses of cinnamtannin A3 (epicatechin pentamer), A4 (e...

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Main Authors:	Kohki Takanashi, Manato Suda, Kiriko Matsumoto, Chisato Ishihara, Kazuya Toda, Koichiro Kawaguchi, Shogo Senga, Narumi Kobayashi, Mikihiro Ichikawa, Miyuki Katoh, Yasunao Hattori, Sei-ichi Kawahara, Koji Umezawa, Hiroshi Fujii, Hidefumi Makabe
Format:	Article
Language:	English
Published:	Nature Publishing Group 2017-08-01
Series:	Scientific Reports
Online Access:	https://doi.org/10.1038/s41598-017-08059-x

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spelling	doaj-2a09a7e1216a434a93e4c8b5322c482c2020-12-08T01:06:32ZengNature Publishing GroupScientific Reports2045-23222017-08-017111310.1038/s41598-017-08059-xEpicatechin oligomers longer than trimers have anti-cancer activities, but not the catechin counterpartsKohki Takanashi0Manato Suda1Kiriko Matsumoto2Chisato Ishihara3Kazuya Toda4Koichiro Kawaguchi5Shogo Senga6Narumi Kobayashi7Mikihiro Ichikawa8Miyuki Katoh9Yasunao Hattori10Sei-ichi Kawahara11Koji Umezawa12Hiroshi Fujii13Hidefumi Makabe14Graduate School of Agriculture, Sciences of Functional Foods, Shinshu UniversityGraduate School of Agriculture, Sciences of Functional Foods, Shinshu UniversityDepartment of Bioscience and Biotechnology, Faculty of Agriculture, Shinshu UniversityDepartment of Biomedical Engineering, Graduate School of Science and Technology, Shinshu UniversityDepartment of Bioscience and Biotechnology, Faculty of Agriculture, Shinshu UniversityInterdisciplinary Graduate School of Science and Technology, Shinshu UniversityInterdisciplinary Graduate School of Science and Technology, Shinshu UniversityDepartment of Biomedical Engineering, Graduate School of Science and Technology, Shinshu UniversityGraduate School of Agriculture, Sciences of Functional Foods, Shinshu UniversityGraduate School of Agriculture, Sciences of Functional Foods, Shinshu UniversityCenter for Instrumental Analysis, Kyoto Pharmaceutical UniversityInterdisciplinary Graduate School of Science and Technology, Shinshu UniversityDepartment of Biomedical Engineering, Graduate School of Science and Technology, Shinshu UniversityDepartment of Biomedical Engineering, Graduate School of Science and Technology, Shinshu UniversityGraduate School of Agriculture, Sciences of Functional Foods, Shinshu UniversityAbstract Since procyanidins (oligomeric catechin or epicatechin) were reported to exhibit health benefits, much attention has been paid to the synthesis of these compounds, especially those that are longer than trimers. In the present study, syntheses of cinnamtannin A3 (epicatechin pentamer), A4 (epicatechin hexamer), catechin tetramer, pentamer, arecatannin A2 (epicatechin-epicatechin-epicatechin-catechin) and A3 (epicatechin-epicatechin-epicatechin-epicatechin-catechin) were achieved. The key reaction was a Lewis acid mediated equimolar condensation. The antitumor effects of these synthesized compounds against a human prostate cancer cell line (PC-3) were investigated. Among the tested compounds, cinnamtannin A3, A4 and arecatannin A3, which possess epicatechin oligomers longer than tetramers as the basic scaffold, showed significant activities for suppression of cell growth, invasion and FABP5 (fatty acid-binding protein 5) gene expression. Effects on cell cycle distribution showed that cell cycle arrest in the G2 phase was induced. Furthermore, these epicatechin oligomers suppressed significantly the expression of the cancer-promoting gene, FABP5, which is related to cell proliferation and metastasis in various cancer cells. Interestingly, the suppressive activities were associated with the degree of oligomerization of epicatechin. Thus, synthetic studies clearly demonstrate that epicatechin oligomers longer than trimers have significant anti-tumorigenic activities, but not the catechin counterparts.https://doi.org/10.1038/s41598-017-08059-x
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Kohki Takanashi Manato Suda Kiriko Matsumoto Chisato Ishihara Kazuya Toda Koichiro Kawaguchi Shogo Senga Narumi Kobayashi Mikihiro Ichikawa Miyuki Katoh Yasunao Hattori Sei-ichi Kawahara Koji Umezawa Hiroshi Fujii Hidefumi Makabe
spellingShingle	Kohki Takanashi Manato Suda Kiriko Matsumoto Chisato Ishihara Kazuya Toda Koichiro Kawaguchi Shogo Senga Narumi Kobayashi Mikihiro Ichikawa Miyuki Katoh Yasunao Hattori Sei-ichi Kawahara Koji Umezawa Hiroshi Fujii Hidefumi Makabe Epicatechin oligomers longer than trimers have anti-cancer activities, but not the catechin counterparts Scientific Reports
author_facet	Kohki Takanashi Manato Suda Kiriko Matsumoto Chisato Ishihara Kazuya Toda Koichiro Kawaguchi Shogo Senga Narumi Kobayashi Mikihiro Ichikawa Miyuki Katoh Yasunao Hattori Sei-ichi Kawahara Koji Umezawa Hiroshi Fujii Hidefumi Makabe
author_sort	Kohki Takanashi
title	Epicatechin oligomers longer than trimers have anti-cancer activities, but not the catechin counterparts
title_short	Epicatechin oligomers longer than trimers have anti-cancer activities, but not the catechin counterparts
title_full	Epicatechin oligomers longer than trimers have anti-cancer activities, but not the catechin counterparts
title_fullStr	Epicatechin oligomers longer than trimers have anti-cancer activities, but not the catechin counterparts
title_full_unstemmed	Epicatechin oligomers longer than trimers have anti-cancer activities, but not the catechin counterparts
title_sort	epicatechin oligomers longer than trimers have anti-cancer activities, but not the catechin counterparts
publisher	Nature Publishing Group
series	Scientific Reports
issn	2045-2322
publishDate	2017-08-01
description	Abstract Since procyanidins (oligomeric catechin or epicatechin) were reported to exhibit health benefits, much attention has been paid to the synthesis of these compounds, especially those that are longer than trimers. In the present study, syntheses of cinnamtannin A3 (epicatechin pentamer), A4 (epicatechin hexamer), catechin tetramer, pentamer, arecatannin A2 (epicatechin-epicatechin-epicatechin-catechin) and A3 (epicatechin-epicatechin-epicatechin-epicatechin-catechin) were achieved. The key reaction was a Lewis acid mediated equimolar condensation. The antitumor effects of these synthesized compounds against a human prostate cancer cell line (PC-3) were investigated. Among the tested compounds, cinnamtannin A3, A4 and arecatannin A3, which possess epicatechin oligomers longer than tetramers as the basic scaffold, showed significant activities for suppression of cell growth, invasion and FABP5 (fatty acid-binding protein 5) gene expression. Effects on cell cycle distribution showed that cell cycle arrest in the G2 phase was induced. Furthermore, these epicatechin oligomers suppressed significantly the expression of the cancer-promoting gene, FABP5, which is related to cell proliferation and metastasis in various cancer cells. Interestingly, the suppressive activities were associated with the degree of oligomerization of epicatechin. Thus, synthetic studies clearly demonstrate that epicatechin oligomers longer than trimers have significant anti-tumorigenic activities, but not the catechin counterparts.
url	https://doi.org/10.1038/s41598-017-08059-x
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Epicatechin oligomers longer than trimers have anti-cancer activities, but not the catechin counterparts

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